Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Proteotoxic Stress and Cell Lifespan Control

  • Cenci, Simone (DiBiT, San Raffaele Scientific Institute and Universita Vita-Salute San Raffaele) ;
  • Pengo, Niccolo (DiBiT, San Raffaele Scientific Institute and Universita Vita-Salute San Raffaele) ;
  • Sitia, Roberto (DiBiT, San Raffaele Scientific Institute and Universita Vita-Salute San Raffaele)
  • Received : 2008.07.12
  • Accepted : 2008.07.14
  • Published : 2008.10.31
⟨ Previous Next ⟩

Abstract

Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to maladaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficult-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell lifespan determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anti-cancer therapies.

Keywords

References

  1. Anelli, T., Alessio, M., Mezghrani, A., Simmen, T., Talamo, F., Bachi, A., and Sitia, R. (2002). ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 21, 835- 844 https://doi.org/10.1093/emboj/21.4.835
  2. Baehrecke, E.H. (2005). Autophagy: dual roles in life and death? Nat. Rev. Mol. Cell Biol. 6, 505-510 https://doi.org/10.1038/nrm1666
  3. Balch, W.E., Morimoto, R.I., Dillin, A., and Kelly, J.W. (2008). Adapting proteostasis for disease intervention. Science 319, 916-919 https://doi.org/10.1126/science.1141448
  4. Benham, A.M., and Sitia, R. (2006). The diversity of oxidative protein folding. Antioxid. Redox Signal, 8, 271-273 https://doi.org/10.1089/ars.2006.8.271
  5. Brewer, J.W., and Hendershot, L.M. (2005). Building an antibody factory: a job for the unfolded protein response. Nat. Immunol. 6, 23-29 https://doi.org/10.1038/ni1149
  6. Cabibbo, A., Pagani, M., Fabbri, M., Rocchi, M., Farmery, M.R., Bulleid, N.J., and Sitia, R. (2000). ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J. Biol. Chem. 275, 4827-4833 https://doi.org/10.1074/jbc.275.7.4827
  7. Cali, T., Galli, C., Olivari, S., and Molinari, M. (2008). Segregation and rapid turnover of EDEM1 by an autophagy-like mechanism modulates standard ERAD and folding activities. Biochem. Biophys. Res. Commun. 371, 405-410 https://doi.org/10.1016/j.bbrc.2008.04.098
  8. Cascio, P., Oliva, L., Cerruti, F., Mariani, E., Pasqualetto, E., Cenci, S., and Sitia, R. (2008). Dampening Ab responses using proteasome inhibitors following in vivo B cell activation. Eur. J. Immunol. 38, 658-667 https://doi.org/10.1002/eji.200737743
  9. Catley, L., Weisberg, E., Kiziltepe, T., Tai, Y.T., Hideshima, T., Neri, P., Tassone, P., Atadja, P., Chauhan, D., Munshi, N.C., et al. (2006). Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 108, 3441-3449 https://doi.org/10.1182/blood-2006-04-016055
  10. Cenci, S., Mezghrani, A., Cascio, P., Bianchi, G., Cerruti, F., Fra, A., Lelouard, H., Masciarelli, S., Mattioli, L., Oliva, L., et al. (2006). Progressively impaired proteasomal capacity during terminal plasma cell differentiation. EMBO J. 25, 1104-1113 https://doi.org/10.1038/sj.emboj.7601009
  11. Chen, Q., Thorpe, J., Ding, Q., El-Amouri, I.S., and Keller, J.N. (2004). Proteasome synthesis and assembly are required for survival during stationary phase. Free Radic. Biol. Med. 37, 859- 868 https://doi.org/10.1016/j.freeradbiomed.2004.05.025
  12. Chondrogianni, N., and Gonos, E.S. (2005). Proteasome dysfunction in mammalian aging: steps and factors involved. Exp. Gerontol. 40, 931-938 https://doi.org/10.1016/j.exger.2005.09.004
  13. Chondrogianni, N., Petropoulos, I., Franceschi, C., Friguet, B., and Gonos, E.S. (2000). Fibroblast cultures from healthy centenarians have an active proteasome. Exp. Gerontol. 35, 721- 728 https://doi.org/10.1016/S0531-5565(00)00137-6
  14. Chondrogianni, N., Stratford, F.L., Trougakos, I.P., Friguet, B., Rivett, A.J., and Gonos, E.S. (2003). Central role of the proteasome in senescence and survival of human fibroblasts: induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation. J. Biol. Chem. 278, 28026-28037 https://doi.org/10.1074/jbc.M301048200
  15. Dice, J.F. (2007). Chaperone-mediated autophagy. Autophagy 3, 295-299 https://doi.org/10.4161/auto.4144
  16. Ding, W.X., and Yin, X.M. (2008). Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome. Autophagy 4, 141-150 https://doi.org/10.4161/auto.5190
  17. Fleming, J.A., Lightcap, E.S., Sadis, S., Thoroddsen, V., Bulawa, C.E., and Blackman, R.K. (2002). Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341. Proc. Natl. Acad. Sci. USA 99, 1461-1466
  18. Fraldi, A., Zito, E., Annunziata, F., Lombardi, A., Cozzolino, M., Monti, M., Spampanato, C., Ballabio, A., Pucci, P., Sitia, R., et al. (2008). Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44. Hum. Mol. Genet. 17, 2610-2621 https://doi.org/10.1093/hmg/ddn161
  19. Gass, J.N., Jiang, H.Y., Wek, R.C., and Brewer, J.W. (2008). The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells. Mol. Immunol. 45, 1035-1043 https://doi.org/10.1016/j.molimm.2007.07.029
  20. Goldberg, A.L. (2003). Protein degradation and protection against misfolded or damaged proteins. Nature 426, 895-899 https://doi.org/10.1038/nature02263
  21. Goldberg, A.L., and Rock, K. (2002). Not just research toolsproteasome inhibitors offer therapeutic promise. Nat. Med. 8, 338-340 https://doi.org/10.1038/nm0402-338
  22. Goodacre, R., Vaidyanathan, S., Dunn, W.B., Harrigan, G.G., and Kell, D.B. (2004). Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 22, 245- 252 https://doi.org/10.1016/j.tibtech.2004.03.007
  23. Gross, E., Sevier, C.S., Heldman, N., Vitu, E., Bentzur, M., Kaiser, C.A., Thorpe, C., and Fass, D. (2006). Generating disulfides enzymatically: reaction products and electron acceptors of the endoplasmic reticulum thiol oxidase Ero1p. Proc. Natl. Acad. Sci. USA 103, 299-304
  24. Hanna, J., and Finley, D. (2007). A proteasome for all occasions. FEBS Lett. 581, 2854-2861 https://doi.org/10.1016/j.febslet.2007.03.053
  25. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889 https://doi.org/10.1038/nature04724
  26. Hideshima, T., Bradner, J.E., Wong, J., Chauhan, D., Richardson, P., Schreiber, S.L., and Anderson, K.C. (2005). Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc. Natl. Acad. Sci. USA 102, 8567-8572
  27. Iwata, A., Riley, B.E., Johnston, J.A., and Kopito, R.R. (2005). HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. 280, 40282-40292 https://doi.org/10.1074/jbc.M508786200
  28. Johnson, T.E., Cypser, J., de Castro, E., de Castro, S., Henderson, S., Murakami, S., Rikke, B., Tedesco, P., and Link, C. (2000). Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors. Exp. Gerontol. 35, 687-694 https://doi.org/10.1016/S0531-5565(00)00138-8
  29. Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884 https://doi.org/10.1038/nature04723
  30. Levine, B., and Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell 132, 27-42 https://doi.org/10.1016/j.cell.2007.12.018
  31. Lund, J., Tedesco, P., Duke, K., Wang, J., Kim, S.K., and Johnson, T.E. (2002). Transcriptional profile of aging in C. elegans . Curr. Biol. 12, 1566-1573 https://doi.org/10.1016/S0960-9822(02)01146-6
  32. Lundgren, J., Masson, P., Realini, C.A., and Young, P. (2003). Use of RNA interference and complementation to study the function of the Drosophila and human 26S proteasome subunit S13. Mol. Cell. Biol. 23, 5320-5330 https://doi.org/10.1128/MCB.23.15.5320-5330.2003
  33. Lundgren, J., Masson, P., Mirzaei, Z., and Young, P. (2005). Identification and characterization of a Drosophila proteasome regulatory network. Mol. Cell. Biol. 25, 4662-4675 https://doi.org/10.1128/MCB.25.11.4662-4675.2005
  34. Lutz, N.W., Franks, S.E., Frank, M.H., Pomer, S., and Hull, W.E. (2005). Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays. Magma 18, 144-161 https://doi.org/10.1007/s10334-005-0107-7
  35. Ma, Y., and Hendershot, L.M. (2003). The stressful road to antibody secretion. Nat. Immunol. 4, 310-311 https://doi.org/10.1038/ni0403-310
  36. Mannhaupt, G., Schnall, R., Karpov, V., Vetter, I., and Feldmann, H. (1999). Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett. 450, 27-34 https://doi.org/10.1016/S0014-5793(99)00467-6
  37. Manz, R.A., Hauser, A.E., Hiepe, F., and Radbruch, A. (2005). Maintenance of serum antibody levels. Annu. Rev. Immunol. 23, 367-386 https://doi.org/10.1146/annurev.immunol.23.021704.115723
  38. Martinez-Vicente, M., Sovak, G., and Cuervo, A.M. (2005). Protein degradation and aging. Exp. Gerontol. 40, 622-633 https://doi.org/10.1016/j.exger.2005.07.005
  39. Meiners, S., Heyken, D., Weller, A., Ludwig, A., Stangl, K., Kloetzel, P.M., and Kruger, E. (2003). Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of mammalian proteasomes. J. Biol. Chem. 278, 21517-21525 https://doi.org/10.1074/jbc.M301032200
  40. Meister, S., Schubert, U., Neubert, K., Herrmann, K., Burger, R., Gramatzki, M., Hahn, S., Schreiber, S., Wilhelm, S., Herrmann, M., et al. (2007). Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Res. 67, 1783-1792 https://doi.org/10.1158/0008-5472.CAN-06-2258
  41. Mezghrani, A., Fassio, A., Benham, A., Simmen, T., Braakman, I., and Sitia, R. (2001). Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J. 20, 6288-6296 https://doi.org/10.1093/emboj/20.22.6288
  42. Nerini-Molteni, S., Ferrarini, M., Cozza, S., Caligaris-Cappio, F., and Sitia, R. (2008). Redox homeostasis modulates the sensitivity of myeloma cells to bortezomib. Br. J. Haematol. 141, 494-503 https://doi.org/10.1111/j.1365-2141.2008.07066.x
  43. Neubert, K., Meister, S., Moser, K., Weisel, F., Maseda, D., Amann, K., Wiethe, C., Winkler, T.H., Kalden, J.R., Manz, R.A., et al. (2008). The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat. Med. 14, 748-755 https://doi.org/10.1038/nm1763
  44. Nicholson, J.K., Lindon, J.C. and Holmes, E. (1999). 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181-1189 https://doi.org/10.1080/004982599238047
  45. Nicholson, J.K., Connelly, J., Lindon, J.C. and Holmes, E. (2002). Metabonomics: a platform for studying drug toxicity and gene function. Nat. Rev. Drug Discov. 1, 153-161 https://doi.org/10.1038/nrd728
  46. Pagani, M., Fabbri, M., Benedetti, C., Fassio, A., Pilati, S., Bulleid, N.J., Cabibbo, A., and Sitia, R. (2000). Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta)., a human gene induced in the course of the unfolded protein response. J. Biol. Chem. 275, 23685-23692 https://doi.org/10.1074/jbc.M003061200
  47. Pandey, U.B., Batlevi, Y., Baehrecke, E.H., and Taylor, J.P. (2007). HDAC6 at the intersection of autophagy, the ubiquitin-proteasome system and neurodegeneration. Autophagy 3, 643-645 https://doi.org/10.4161/auto.5050
  48. Princiotta, M.F., Finzi, D., Qian, S.B., Gibbs, J., Schuchmann, S., Buttgereit, F., Bennink, J.R., and Yewdell, J.W. (2003). Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18, 343-354 https://doi.org/10.1016/S1074-7613(03)00051-7
  49. Raamsdonk, L.M., Teusink, B., Broadhurst, D., Zhang, N., Hayes, A., Walsh, M.C., Berden, J.A., Brindle, K.M., Kell, D.B., Rowland, J.J., et al. (2001). A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat. Biotechnol. 19, 45-50 https://doi.org/10.1038/83496
  50. Radbruch, A., Muehlinghaus, G., Luger, E.O., Inamine, A., Smith, K.G., Dorner, T., and Hiepe, F. (2006). Competence and competition: the challenge of becoming a long-lived plasma cell. Nat. Rev. Immunol. 6, 741-750 https://doi.org/10.1038/nri1886
  51. Rajkumar, S.V., Richardson, P.G., Hideshima, T., and Anderson, K.C. (2005). Proteasome inhibition as a novel therapeutic target in human cancer. J. Clin. Oncol. 23, 630-639 https://doi.org/10.1200/JCO.2005.11.030
  52. Reo, N.V. (2002). NMR-based metabolomics. Drug Chem. Toxicol. 25, 375-382 https://doi.org/10.1081/DCT-120014789
  53. Rideout, H.J., Lang-Rollin, I., and Stefanis, L. (2004). Involvement of macroautophagy in the dissolution of neuronal inclusions. Int. J. Biochem. Cell Biol. 36, 2551-2562 https://doi.org/10.1016/j.biocel.2004.05.008
  54. Romijn, E.P., Christis, C., Wieffer, M., Gouw, J.W., Fullaondo, A., van der Sluijs, P., Braakman, I., and Heck, A.J. (2005). Expression clustering reveals detailed co-expression patterns of functionally related proteins during B cell differentiation: a proteomic study using a combination of one-dimensional gel electrophoresis, LC-MS/MS, and stable isotope labeling by amino acids in cell culture (SILAC). Mol. Cell Proteomics 4, 1297-1310 https://doi.org/10.1074/mcp.M500123-MCP200
  55. Ruddock, L.W., and Molinari, M. (2006). N-glycan processing in ER quality control. J. Cell Sci. 119, 4373-4380 https://doi.org/10.1242/jcs.03225
  56. Schubert, U., Anton, L.C., Gibbs, J., Norbury, C.C., Yewdell, J.W., and Bennink, J.R. (2000). Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770- 774 https://doi.org/10.1038/35008096
  57. Sciammas, R., and Davis, M.M. (2004). Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation. J. Immunol. 172, 5427-5440 https://doi.org/10.4049/jimmunol.172.9.5427
  58. Shaffer, A.L., Lin, K.I., Kuo, T.C., Yu, X., Hurt, E.M., Rosenwald, A., Giltnane, J.M., Yang, L., Zhao, H., Calame, K., et al. (2002). Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51-62 https://doi.org/10.1016/S1074-7613(02)00335-7
  59. Shapiro-Shelef, M., and Calame, K. (2005). Regulation of plasmacell development. Nat. Rev. Immunol. 5, 230-242 https://doi.org/10.1038/nri1572
  60. Sitia, R., and Braakman, I. (2003). Quality control in the endoplasmic reticulum protein factory. Nature 426, 891-894 https://doi.org/10.1038/nature02262
  61. Troncale, J.A. (1996). The aging process. Physiologic changes and pharmacologic implications. Postgrad. Med, 99, 111-114, 120-122 https://doi.org/10.1080/00325481.1996.11946121
  62. van Anken, E., Romijn, E.P., Maggioni, C., Mezghrani, A., Sitia, R., Braakman, I., and Heck, A.J. (2003). Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity 18, 243-253 https://doi.org/10.1016/S1074-7613(03)00024-4
  63. Wiseman, R.L., Powers, E.T., Buxbaum, J.N., Kelly, J.W., and Balch, W.E. (2007). An adaptable standard for protein export from the endoplasmic reticulum. Cell 131, 809-821 https://doi.org/10.1016/j.cell.2007.10.025
  64. Xie, Y., and Varshavsky, A. (2001). RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit. Proc. Natl. Acad. Sci. USA 98, 3056-3061